Conformational analogy between .beta.-lactam antibiotics and tetrahedral transition states of dipeptide

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Abstract
The 3-dimensional structures of various penicillins and cephalosporins are compared to the spatial characteristics of glycylglycine and the tetrahedral adducts formed when a nucleophile attaches to the amide carbonyl C of this dipeptide. The dipeptide is taken to model the D-alanyl-D-alanine terminus of the precursors of bacterial cell-wall peptidoglycan cross-links. Least-squares fitting shows that the spatial match between the dipeptide and the antibiotic depends on the thiazolidine or dihydrothiazine ring confirmation and the conformation of the dipeptide. In general, the tetrahedral adducts fit somewhat better than the parent dipeptide. A previously unobserved 3-cephem conformer is found by molecular mechanics calculations to be less stable than the usual crystallographically observed conformer.